Laucht Manfred, Treutlein Jens, Schmid Brigitte, Blomeyer Dorothea, Becker Katja, Buchmann Arlette F, Schmidt Martin H, Esser Günter, Jennen-Steinmetz Christine, Rietschel Marcella, Zimmermann Ulrich S, Banaschewski Tobias
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
Biol Psychiatry. 2009 Jul 15;66(2):102-9. doi: 10.1016/j.biopsych.2009.02.010. Epub 2009 Apr 9.
Evidence from animal studies supports a role for serotonin transporter gene promoter polymorphism (5-HTTLPR) gene-environment interaction (G x E) in the development of excessive alcohol intake. Few studies in humans have been conducted on this topic, yielding inconsistent results. The present study aims to further explore G x E between 5-HTTLPR and exposure to psychosocial adversity on alcohol consumption in a high-risk community sample of young adults.
Data were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study following the outcome of early risk factors from birth into young adulthood. At age 19 years, 309 participants (142 male participants, 167 female participants) were genotyped for the biallelic and triallelic 5-HTTLPR and were administered a 45-day alcohol timeline follow-back interview, providing measures of the total number of drinks and the number of binge drinking days. Psychosocial adversity was assessed at birth (family adversity) and at age 19 (negative life events).
In contrast to various previous reports, a significant G x E emerged, indicating that, when exposed to high psychosocial adversity, individuals with the LL genotype of 5-HTTLPR exhibited more hazardous drinking than those carrying the S allele or those without exposure to adversity. This effect, which was confined to male participants, held both for different classifications of 5-HTTLPR and different types of adversity.
One explanation for the discrepant results might be heterogeneity in alcohol phenotypes. While the L allele relates more strongly to early-onset alcoholism, the S allele may be linked more closely to alcohol use associated with anxiety and depression.
动物研究的证据支持血清素转运体基因启动子多态性（5-HTTLPR）基因-环境相互作用（G×E）在过量饮酒发展过程中的作用。关于这一主题，人类研究较少，结果也不一致。本研究旨在进一步探讨在高危社区年轻成年人样本中，5-HTTLPR与心理社会逆境暴露之间的基因-环境相互作用对饮酒的影响。
数据收集是曼海姆高危儿童研究的一部分，这是一项正在进行的流行病学队列研究，追踪从出生到青年期早期危险因素的结果。19岁时，对309名参与者（142名男性参与者，167名女性参与者）进行双等位基因和三等位基因5-HTTLPR基因分型，并进行为期45天的酒精使用时间线随访访谈，提供饮酒总量和暴饮天数的测量数据。心理社会逆境在出生时（家庭逆境）和19岁时（负面生活事件）进行评估。
与之前的各种报告不同，出现了显著的基因-环境相互作用，表明当暴露于高心理社会逆境时，5-HTTLPR基因LL基因型的个体比携带S等位基因的个体或未暴露于逆境的个体表现出更危险的饮酒行为。这种效应仅限于男性参与者，在5-HTTLPR的不同分类和不同类型的逆境中均成立。
结果差异的一种解释可能是酒精表型的异质性。虽然L等位基因与早发性酒精中毒的关系更强，但S等位基因可能与焦虑和抑郁相关的饮酒行为联系更紧密。
